Focus on the frontier, deep interpretation, and chew the literature to get the essence of the "shower"

The "Fine Chew literature - a series of activities for young and middle-aged doctors to read lymphoma literature" was jointly led by Professor Zhang Huilai of The Cancer Hospital of Tianjin Medical University and Professor Zou Dehui of the Hematology Hospital of the Chinese Academy of Medical Sciences

Since 2020, 33 issues have been held, and each issue has been deeply interpreted, and a number of young scholars have been invited to interpret the latest research progress of various types of lymphoma from different angles, and many well-known experts have made wonderful comments, and the response in the field of lymphoma has been enthusiastic

Chew literature (1)

Trends in Late Mortality and Life Expectancy After Autologous Blood or Marrow Transplantation Over Three Decades: A BMTSS Report

>>>>

Highlights are presented

• The overall survival rate for patients at 25 years was 41%, and life expectancy was reduced by 26% compared to the general population, that is, life expectancy was shortened by 7 years

  
  

• Long-term mortality in patients with autologous BMT is on a downward trend

  
  

Big coffee reviews

Professor Shen Xuliang pointed out that with the emergence of many new drugs, autologous hematopoietic stem cell transplantation (ASCT) should be repositioned

CAR T-cells as a second-line therapy of large B-cell lymphoma:A paradigm shift?

In this paper, the three classic studies of CAR-T therapy, Belinda, ZUMA-7 and Transformer, were mainly analyzed to compare the efficacy and safety
of second-line CAR-T therapy and standard treatment regimens in patients with high-risk relapsed/refractory large B-cell lymphoma (R/R LBCL).

>>>>

Highlights are presented

• In this paper, the three classic studies of CAR-T therapy, Belinda, ZUMA-7 and Transformer, were mainly analyzed to compare the efficacy and safety
  of second-line CAR-T therapy and standard treatment regimens in patients with high-risk relapsed/refractory large B-cell lymphoma (R/R LBCL).
  

• In three studies, zuMA-7 and Transformer achieved the primary endpoint of improving event-free survival (EFS), which was extended by about 6 and 8 months, respectively, compared with the standard treatment group and the CAR-T treatment group; The Belinda study showed a similar median EFS of 3 months
  in both groups.
  
  Inconsistent results are considered to be related
  to differences in study design.
  

• The results of the ZUMA-7 and Transformer studies demonstrate that second-line CAR-T therapy can be tried in patients with LBCL who are refractory or relapse within 1 year of completing first-line therapy
  .
  
  Negative results observed in the Belinda study suggest delayed or given CAR-T therapy in poorly controlled settings, which may affect efficacy
  .
  

Big coffee reviews

The recommendation of CAR-T therapy in this study, in addition to its better efficacy, is more likely to be due to a higher proportion of people who can receive CAR-T treatment and a wider range
of beneficiaries.

Professor Zou Dehui believes that taking recurrence or refractory treatment within 1 year as the basis for choosing CAR-T treatment has certain limitations, the real situation will be more complicated, and there are more
problems to consider.

Professor Liu Yang said that with the current research evidence, polatuzumab may be a better choice for bridging therapy, even if the bridging treatment has failed and has not received CAR-T treatment, through the polaruzumab-based treatment, it can also give patients the opportunity to
get CAR-T treatment or ASCT.

Genomic and transcriptomic profiling reveals distinct molecular subsets associated with outcomes in mantle cell lymphoma
analysis of different molecular subsets associated with MCL prognosis

In this paper, MCL is divided into four types of C1-C4 according to the different mutation sites, and the effects
of different types on prognosis are studied.

>>>>

Highlights are presented

• C1 has immunoglobulin heavy chain variable region (IGHV) mutations, CCND1 mutations, amp (11q13), and active B cell receptor (BCR) signals
  .
  
  C2 is rich in del(11q)/ATM mutations and NF-κB upregulation as well as DNA repair pathways
  .
  
  C3 is characterized by SP140, NOTCH1, and NSD2 mutations, BCR signaling, and DOWN-regulation of myC targets
  .
  
  C4 contains del(17p)/TP53 mutations, del(13q) and del(9p), as well as active MYC pathways and overproliferation characteristics
  .
  
  The prognosis varied among the four groups, with 5-year overall survival rates of 100%, 56.
  7%, 48.
  7%, and 14.
  2%,
  respectively.
  
  

• TP53 mutations are a poor prognostic factor for most blood tumors
  .
  
  Both C1 and C4 contain TP53 mutations (36% and 63%), but prognosis varies widely, and considering the association of mutations in TP53 with clinical outcomes is more likely to depend on the effects
  of simultaneous genetic events.
  

• A large number of somatic copy number variants (SCNA) are associated
  with poorer overall survival (OS).
  
  

Big coffee reviews

For incurable diseases such as MCL, it is very meaningful
to explore molecular typing, preliminarily judge the prognosis of patients, and guide treatment medications.

However, how to apply the basic research results well in the clinic is another difficult challenge
.

Taking TP53 as an example, even if there is also a TP53 mutation, the prognosis is very different in different molecular typing, so Professor Zhang Huilai suggested that pathological typing and molecular typing can be organically combined to study, or more clinically meaningful conclusions can be obtained
.

Exploring the molecular typing of refractory diseases and simplifying the analysis process to make it easy to apply to the clinic and achieve precision treatment may be the direction of
future research.

Mantle cell lymphoma in 2022 -A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments
2022 MCL Molecular Pathogenesis, Comprehensive update of diagnosis, risk stratification and treatment strategies

This paper mainly provides a comprehensive update
on the pathogenesis, diagnosis, prognostic factors, and treatment of MCL.

  

>>>>

Highlights are presented

• Patients with MCL should pay attention to the comprehensive evaluation at the first diagnosis, and the treatment decision
  should be decided according to the clinical category of the patient.
  
  

• Traditional chemotherapy is gradually being replaced
  by Chemo-free oral-targeted drugs.
  
  

• Triple-resistant relapsed/refractory MCL is highly refractory and treatment options are limited, and patients are recommended to participate in clinical studies
  .
  
  

• Anti-ROR1 antibodies - drug conjugates, non-covalent BTKi, Bcl2 inhibitors, bispecific antibodies (such as Glossamab, Mosunetuzumab, polatuzumab, etc.
  ), CAR-T is very promising
  .
  
  

Big coffee reviews

Although the current guidelines recommend CAR-T for third-line treatment, Professor Zhang Believes that in diffuse large B-cell lymphoma (DLBCL), for high-risk patients, CAR-T may be considered to advance CAR-T to first-line or 1.
5-line treatment
.

For high-risk patients with MCL, the effect of traditional treatment and the addition of new drugs are not satisfactory, and whether the use of CAR-T treatment in advance can bring more benefits to patients is worth exploring and looking forward to
.

Impact of Etoposide and ASCT on Survival Among Patients <65 years With Stage II-IV PTCL; Effect of a Population-Based Cohort Study
etoposide and ASCT on survival in patients with stage II-IV PTCL aged < 65 years

In this paper, we mainly retrospectively analyzed the patient data of stage II-IV adult (18-65 years) PTCL, and explored the effect
of etoposide and ASCT on the overall survival of patients with PTCL.

>>>>

Highlights are presented

• 1427 patients with peripheral T-cell lymphoma (PTCL) were screened and divided into etoposide pre-era (1989-2008) and post-epoch (2009-2018) based on 2008, and the 5-year OS significantly increased from 39% of the previous era to 49% of the post-era, indicating that the application of etoposide and ASCT can improve the survival of
  patients.
  
  

• Patients treated with CHOP (CHOP + etoposide) had a 5-year OS superior to those treated with CHOP (59% vs.
  38%), but the risk of death was similar in patients treated with CHOP and CHOEP when age, PTCL subtype, International Lymphoma Prognosis Index (IPI) score, and ASCT as a time-varying covariate were corrected
  .
  
  

• Using milestone (9 months post-diagnosis as a new starting point for follow-up) analysis, 5-year OS was superior to patients undergoing consolidation therapy with ASCT over patients with induction chemotherapy alone (78% vs.
  45%)
  .
  
  

Big coffee reviews

This study is based on a nationwide population study and provides evidence to support
the application of etoposide and ASCT to PTCL.

Professor Zou Dehui pointed out that most of the current research focuses on new drugs, new therapies, etc.
, although it is relatively easy to make breakthroughs, but for existing treatment effects are not ideal, or treatment methods are controversial diseases, such as PTCL, through the national large retrospective study, analysis and comparison of the advantages and disadvantages of existing therapies, can give clear answers to treatment-related questions, still have high value
.

Chew literature (VI) 1.
The ECHELON-2 Trial: 5-year results of a randomized, phase lll study of BV with chemotherapy for CD30-positive peripheral T-cell lymphoma
Results of a randomized, phase III study of BV combined with chemotherapy in the treatment of CD30-positive PTCL2.
Role of Stem Cell Transplant in CD30-positive PTCL following Frontline BV+CHP or CHOP in ECHELON-2
BV+CHP or CHOP in CD30-positive PTCL treatment after hematopoietic stem cell transplantation

The two articles are analyses
of different phases of the same study (ECHELON-2).

The former compared the efficacy of A+ CHP and CHOP in untreated patients with PTCL, while the latter analyzed the role of
hematopoietic stem cell transplantation (SCT) in patients with PTCL.

>>>>

Highlights are presented

• A total of 452 untreated patients with CD30-positive PTCL aged ≥ 18 years were enrolled, with a median follow-up time of 47.
  6 months
  .
  
  The 5-year progression-free survival (PFS) rates in the A+CHP group and CHOP were 51.
  4% and 43.
  0%, respectively, the 5-year OS rates were 70.
  1% and 61.
  0%, and the peripheral neuropathy remission or improvement
  was 72% and 78%, respectively.
  
  In patients who relapsed and subsequently received BV treatment, the objective effectiveness rate of retherapy in the A+ CHP group was 59%, and the objective effectiveness rate of retherapy in the CHOP group was 50%.
  
  
  

• Patients who received SCT had a 64% lower risk of developing a PFS event, with median PFS not reaching, compared with a median PFS of 55.
  66 months
  in patients who did not receive SCT.
  
  Results supported SCT
  in ALK-negative anaplastic large cell lymphoma (ALCL) and non-ALCL subpopulations.
  
  These data support the consideration of SCT in CD30-positive patients with CTCl after complete remission (CR) with A+CHP
  .
  
  

• It can be seen that transplantation still occupies an important position
  in PTCL treatment.
  
  

Big coffee reviews

At present, transplantation still occupies an important position in PTCL treatment, and better first- or second-line treatment options need to be explored for different molecular mechanisms
.

Professor Zhang Huilai suggested that only by taking precise treatment according to the different molecular typings of PTCL can patients have more survival benefits
.

For patients with PTCL, if good remission cannot be achieved in first- or second-line treatment, the subsequent treatment effect will be relatively poor, so it is necessary to pay attention to the rational choice
of early treatment options.

Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma
ibutinib combined with bendamustine and rituximab in the treatment of initial MCL This article mainly compares the efficacy of ibrutin plus bendamustine and rituximab (BR) or placebo + BR in the treatment of primary MCL
。

>>>>

Highlights are presented

• A total of 589 elderly patients aged ≥ 65 years were screened, with a median follow-up time of 84.
  7 months, ibutinib group with 80.
  6 months of moderate PFS, and placebo group with 52.
  9 months, suggesting that combined with ibtinib on a BR basis significantly prolonged patient median PFS to nearly 7 years, compared with the placebo group by 2.
  3 years
  .
  
  

• Ibltinib was 55% OS at 7 years and 56.
  8% in the placebo group, and there was no significant difference between
  the two groups.
  
  

• 11.
  5% of patients in the ibutinib group died due to disease progression, compared with 20.
  6% in the placebo group; Among those who died because of treatment-related adverse events, 10.
  7% in the ibtenib group and 6.
  1%
  in the placebo group.
  
  

Big coffee reviews

Although the study showed a significant prolongation of PFS in the ibrutinib group, it also suggested a significant increase in adverse reactions in patients in this group, especially during the maintenance treatment phase
.

Professor Zhang Huilai reminded that the quality
of life of patients should not be reduced in order to pursue longer PFS.

In order to reduce the incidence of adverse reactions of ibutinib, further exploration
of its therapeutic dose and course of treatment may be required in the future.

At the same time, when selecting patients using ibrutinib combined with br protocol, it is recommended to first assess their physical condition, and high-risk patients may not be suitable for this regimen
.

In addition, during the maintenance phase of ibutinib, intensive supportive care may be required
.

Chew literature (VIII) 1.
Genomic profiling identifies distinct genetic subtypes in extranodal natural killer/T-cell lymphoma
Genomic and Transcriptomic Characterlzation of Natural Killer T Cell Lymphoma
NK/T cell lymphoma genomic and transcriptome characterization analysis

Both articles analyzed the genotypes of patients with NK/T cell lymphoma (NKTCL) to identify significant differences in treatment response and prognosis of different subtypes
.

>>>>

Highlights are presented

• The genotypes of 209 patients with extranodal nasal NK/T cell lymphoma (ENKTCL) were analyzed and seven subtypes were proposed, and the clinical prognosis of different subtypes was significantly different
  .
  
  IPI, site of disease, stage, and presence of intranosicular lesions and hepatosplenomegaly are clearly correlated
  with the overall survival of patients with ENKTCL.
  
  Genetic profiles of ENTKCL from Asian and Hispanic populations show striking similarities, suggesting that the two groups share a common pathogenesis and tumor evolutionary processes
  .
  
  

• Three main subtypes were defined in 128 NKTCL biopsy samples, with significant differences in origin cells, EBV gene expression, transcriptional signatures, and response to treatment, suggesting the possibility of potential therapeutic targets
  .
  
  

Big coffee reviews

Professor Zhang Huilai pointed out that pathological typing is the foundation, molecular typing can not override the pathological typing, and molecular typing cannot be used to replace pathological typing
.

To conquer tumors, immunotherapy may be an important direction
.

But at present, for some refractory diseases, such as NKTCL, there is no good immunotherapy.


In this case, in-depth study of the molecular typing of these intractable diseases may provide better guidance for clinical treatment and can also guide the next step of targeted therapy research on
NKTCL.

summary

Many young talents carefully selected high-quality research and review literature, and made a comprehensive and detailed exposition of lymphoma from different perspectives, different fields and different levels, and listened to it clearly, believing that through in-depth sharing and discussion, it can help clinicians to broaden their horizons and further improve the level
of lymphoma diagnosis and treatment in China.

It is expected that young doctors in the follow-up activities will be able to provide more high-quality literature interpretations to optimize
clinical practice and benefit the majority of patients.

REVIEW Past Review1
,

Talents gathered, chewed on the literature, and worked together to discuss the way to heal the "shower"

Reviewed: Janet Typesetting: Moly Executive: Wenting

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